OBJECTIVES: 1. To continue the investigation into the physiological roles of the endogenous opioid peptides, methionine-enkephalin, leucine-enkephalin and beta-endorphin. 2. To study the interaction of the opioid peptides with the different opiate receptors by the use of four parallel assays; the guinea-pig ileum, mouse vas deferens and the inhibition of (3H)-dihydromorphine and (3H)-D-Ala2-D-Leu5-enkephalin binding in brain homogenates. To examine the usefulness of these assays for the design of new stable analogues of the natural enkephalins. 3. To study the differential distribution in the dentral and peripheral nervous systems of mu-opiate receptors, represented by (3H)-dihydromorphine binding sites and delta-opiate receptors, represented by (3H)-D-Ala2-D-Leu5-enkephalin binding sites. 4. To study the biosynthesis of methionine- and leucine-enkephalin and to define the nature and characteristics of their precursors. 5. To study the conditions of the release of the enkephalins. 6. To continue the investigation of the role of the interaction between the endogenous opioid peptides and exogenously applied narcotic analgesics in the development of tolerance and dependence. 7. To continue to assess the agonist and antagonist characteristics of new synthetic narcotic analgesic drugs and to study their affinities to the several opiate receptors by means of the four parallel assays described in paragraph 2.